Geen technologies for the extraction of antioxidant compounds from natural sources.
\r\n\tIncreasingly, governments and development institutions are recognizing the importance of addressing social exclusion for sustainable development. As such, the book will examine the role of government and the contribution of international development partners in the protection and support of marginalized groups and communities. Additionally, the role, responsibility, and response of academia as a socially accountable partner will form part of the discourse.
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Nowadays, the awareness for the need to have a healthier lifestyle results in a higher consumption of natural organic food products and nutritionally rich antioxidants rather than synthetic and processed foods. In the past decade, an increased interest in the exploitation of natural ingredients to be used in the food and food products was observed. Researchers from all over the world are focusing on alternative sources of healthy nutrients promoting a safer and convenient diet. There is not clear evidence that synthetic antioxidants have toxic effects, although, consumer’s interest is moving towards the natural products. Moreover, synthetic antioxidants and preservatives in food may lead to lipid peroxidation and deterioration of food flavor and quality [1]. Therefore, organic and sustainable processes, the identification of new phytochemicals with attractive biological activities, such as antioxidant, anticancer, antimicrobial, among others, are a hot topic among food researchers as well as for food industry aiming to develop new functional and therapeutic products.
Natural antioxidants are mainly derived from food, plants and other living organisms, such as fruits, vegetables, flowers, cereals, mushrooms, macro and micro-algae, spices and traditional medicinal herbs [2]. It is known that exogenous antioxidants have a strong potential to inhibit oxidative stress, preventing the lipid peroxidation process, and restore the cellular homeostasis [3]. Indeed, most of the antioxidant products shown to act as potential therapeutic agents. The consumption of antioxidants is highly important not only in prevention but also as an adjunct in the treatment of various human pathologies associated with oxidative stress, such as diabetes, aging, neurological, cardiovascular, and cancer [4]. In this sense, beneficial health effects of antioxidants are directly linked to regular daily intake and bioavailability.
The issues created by the increase of the human population, together with a reduction in renewable resources, is reflected in the increase of the global demand for reuse of industrial biowastes, as well as increasing the use of underexploited resources. The growing demand for new or alternative bioactive molecules obtained by green and sustainable processes, and decreasing the quantity of biowastes are premises for the development of conscious approaches for the valorization of phytochemicals from natural sources [5, 6]. Additionally, the development and optimization of efficient and intensified process for the recovery and isolation of high value phytochemicals are important.
The current chapter is focused on appreciation of different green extraction strategies related to the recovery of high value bioactive compounds from natural sources, their potential antioxidant activity, and possible nutritional and health applications.
The recovery of antioxidant biomolecules or extracts is an important step to enable the reuse of natural resources for subsequent application in pharmaceutical, cosmetic products, food enrichment and preservatives, supplements and nutraceuticals.
Usually, bioactive phytochemicals are obtained using solid–liquid extraction, the unit operation, and depends on several factors, including the applied extraction technique, the parameters associated with the technique (such as temperature, time, pH and the extraction solvent), and the raw materials composition [7]. Extraction process is composed by 4 essential steps: (1) raw material pre-treatment (drying, grinding,
The extraction process, when it is not optimized, is often time and energy consuming, induces the use of huge amount of water or petroleum-based solvents (harmful for environment and consumers) and generates large quantity of waste [9]. Moreover, the resulting extract may not be safe for the consumers, as it may contain residual solvents, contaminants from raw material, or denatured compounds due to extreme extraction conditions [5]. In this sense, the extraction processes intensification/optimization is necessary. The goal of an intensified process is to obtain greater extraction efficiency, high-quality and safe extracts while reducing extraction time, energy consumption, number of unit operations, amount of water and organic solvents in the process, environmental impact, economic costs and quantity of waste generated [8].
In the last decades, the growing interest in the global ecological footprint reduction, bioeconomy control and consumer safety, has propel the implementation of innovative and clean alternatives in the food, chemical, cosmetic and pharmaceutical industries, following the principles of green chemistry and green engineering [10, 11].
Among the various extraction factors, solvents play an important role in extraction efficiency. The reduction of hazardous solvents is also considered one of the priorities of international policies [12]. A suitable solvent is able to obtain safe and high-quality ingredients and to preserve the biological effects of the extracted compounds. Furthermore, it should be recyclable and reusable, preventing negative environmental effects.
Numerous solvents have been used for the extraction of antioxidants from foods, marine sources, medicinal plants and agroindustrial wastes [6]. The selection of solvents must be based on the chemical nature and polarity of the compounds to be extracted, since solvents with different polarities are necessary for the isolation of compounds with different chemical structure [5]. For example, most of the phenolics, flavanoids and anthocyanins are hydrosoluble antioxidants. The polar and medium polar solvents, such as water, ethanol, methanol, propanol, acetone and their aqueous mixtures, are widely used for their extraction [13, 14, 15]. Carotenoids are lipid-soluble antioxidants, and common organic solvents, such as the mixtures of hexane with acetone, ethanol, methanol, or mixtures of ethyl acetate with acetone, ethanol, methanol, have been used for extraction [16, 17, 18].
A number of new alternatives to conventional techniques (Soxhlet, heat reflux, infusion, distillation,
Extraction technology | Concept | Advantages | Disadvantages | References |
---|---|---|---|---|
Microwave assisted extraction (MAE) | Microwaves are electromagnetic fields in the range of 300 MHz to 300 GHz. The solvent penetrates into the solid matrix by diffusion leading to cell disruption and releasing the compounds of interest from a matrix to a solvent. | Lower time of extraction; low solvent volume; effective, uniform and selective heating. | High extraction pressure might modify the chemical structures of the compounds; low penetration of radiation in bulk products; equipment more expensive. | [5, 19] |
Ultrasound assisted extraction (UAE) | Ultrasound is a sound wave of 20 kHz to 100 MHz. This process produces a phenomenon called cavitation, which means that the production, growth, and collapse of the bubbles to form pores that facilitate the cell wall disruption and increased the release of intracellular compounds into the extraction medium. | Fast; low solvent usage; lower extraction temperatures; preserving heat-sensitive compounds; eco-friendly and cheap process. | Energy intensive; dificult to scale up. | [20, 21] |
Pressurized liquid extraction (PLE) | This technology is based on the use of liquid solvents at temperature and pressure values above the atmospheric boiling point and below the critical point values, decreasing the viscosity of the solvent, promoting accelerated dissolution kinetics, and increasing the solutes’ solubility. The process disrupts the matrix, which increases the mass transfer of the analyte from the solvent sample | Rapid extraction; reduced organic solvent consumption. | Requires sophisticated instrumentation; possible degradation of thermolabile compounds. | [22, 23] |
Supercritical fluid extraction (SFE) | Supercritical extraction is characterized by changes in temperature and pressure which transform the gas in supercritical fluid. | Fast; selective extraction; no residual solvents. | High cost; energy intensive; low polarity; type of co-solvent affects the efficiency of the extraction of antioxidant compounds. | [23, 24] |
High hydrostatic pressure (HHP) | This technology applys very high pressures (100–1000 MPa) at 0 °C to less than 100 °C for a short period of time. Improves mass transfer rates and increases the secondary metabolite diffusion according to phase transitions. | Time efficient, requires less solvent, convenient, eco-friendly, safe and energy efficient; does not generate waste; pure and microbiologically safe products; absence of heating, avoiding compound denaturation and ensuring the extraction of thermo-sensitive components. | Variable efficiency; high processing costs. | [25, 26, 27, 28] |
Enzyme assisted extraction (EAE) | The matrix and enzyme solution are loaded into an extraction vessel and placed in a thermostated water bath at the certain temperature and time. | Moderate extraction conditions; eco-friendly; selectivity due to the specificity of enzymes. | Expensive cost of enzymes; activity of enzymes varying with the environmental factors; filtration and cleanup step required; time consuming. | [3, 7, 23] |
Pulsed electric field (PEF) | The material is placed between two electrodes. The pulse amplitude varies from 100–300 V/cm to 20–80 kV/cm. The treatment is conducted at room temperature or slightly higher. The principle of PEF extraction is to induce the electroporation of the cell membrane, thereby increasing the extraction yield. | Improves extraction and diffusion; cell permeability; minimize loss of heat sensitive molecules; selectivity of extracted compounds. | High control of parameters associated with the process (energy input, strength, pulses, temperature, and raw material properties, | [5, 9, 29, 30] |
High voltage electrical discharges (HVED) | It is an effective method to damage the cell structure and the extraction of valuable cellular compounds. The first step is the formation and propagation of a coil of a needle electrode and the formation of gaseous cavities. The second stage occurs when the streamer reaches the electrode plate (phase decomposition). | Efficiency of cell destruction; low solvent consumption; low operating temperature and temperature rise. | Free radicals production, which can react with antioxidant compounds, thus decreasing their bioactivy; lower selectivy; scale-up difficulties. | [19, 22, 31] |
Ohmic heating (OH) | Non-pulsed electrotechnology centered on the conversion of electric energy into thermal energy based in the Joule effect (heat is generated inside a conductive matrix). The voltage applied in the OH process normally varies between 400 and 4000 V (electric field from 0.001 to 1 kV/cm). | Fast and homogeneous heating; reduction of energy consumption and times; low water and organic solvents use; low waste generation; selectivity of extracted compounds; improves extraction and diffusion by cell permeability. | High control of parameters associated with the process (similar to PEF and HVED). | [9, 32, 33] |
Geen technologies for the extraction of antioxidant compounds from natural sources.
In the following sections some examples of natural matrices used as sources of antioxidant compounds using clean and innovative processes will be reported.
Fruits and vegetables are highly recommended dietary contents, widely known for their health-promoting effects and nutritious values. They got an essential place as conventional foods in the history because of their high amount of minerals, specifically electrolytes; vitamins, mainly vitamins C and E. Several studies are also demonstrating their high phytochemical contents eith antioxidant properties. Antioxidants obtained from plants, vegetables and fruits are mostly of terpenes, polyphenols, phytosterols, peptides, vitamins and minerals (Figure 1) [34, 35]. Antioxidant minerals, such as iron, zinc, selenium, copper, and manganese, act as cofactor of many antioxidant enzymes, absence of which may certainly disturb the activity of their enzymatic scavenging activity [2].
Classification of natural antioxidants.
It has been argued that agri-food residues generated by the use of plants and their derivatives might have a negative impact on the environment when they are discarded. In developed countries, 42% of food waste is produced by households, while 39% losses occur in the food manufacturing industry, 14% in food service sector and remaining 5% in retail and distribution [36]. Waste from parts of plants such as peel, leaves, stem, seed, and roots generated from agriculture, to industrial manufacturing and processing [2]. They constitute a low-cost source of antioxidant molecules, which exhibit other biological activities, like antidiabetic, anti-obesity, antihypertensive, anticancer, and antimicrobial [13, 37, 38].
Marine biodiversity is another underexploited source of natural products. Marine resources are gaining the attention of industries such as foods, pharmaceuticals, nutraceuticals, and cosmetics because they have several interesting antioxidant molecules and other attractive biotechnological compounds (
Algae are considered the richest source of active compounds with antioxidant activity (and other biological activities). They can be used as nutraceuticals, food additives and cosmetics. Algae are composed by a complex group of photosynthetic organisms with simple reproductive organs, which can be multicellular, known as macroalgae or seaweeds, and unicellular named as microalgae [40]. Algae produce various secondary metabolites with many antioxidant activities such as pigments (phycobiliproteins, chlorophylls and carotenoids), polyphenols (bromophenols, flavonoids, phlorotannins and phenolic acids), vitamins (β-carotene and other carotenoids), a complex of B vitamins (B1, B2, B3, B5, B6, B7 and B12), vitamin C (ascorbic acid), vitamin D and vitamin E (α-tocopherol) [40, 41]. Sulfated polysaccharides are nonanimal compounds reported to have antioxidant activities, which can be obtained from marine algae and other marine organisms from the phaeophyta group [42]. These compounds may be used as hydrocolloids and as nutraceuticals in the food industry.
Iodine (an important mineral from seaweeds), is a key element for hormones related with the thyroid, helping in the metabolism regulation [43].
Marine sponges (family Aplysinellidae) are recognized as producers of bromotyrosine derivatives, displaying a myriad of biological and pharmacological potentialities [39]. Many biological compounds previously isolated from some other marine organisms such as fish, crustaceans, and their by-products present bioactive potential.
For the past few decades, researchers and industry have been focusing their work on the use of by-products or biowastes to obtain products with high added value, using innovative and environmentally friendly processes. These products can be used as (bio)functional additives, or as a therapeutic alternative in the prevention or treatment of cardiometabolic, cancer and neurodegenerative diseases [40, 42, 44, 45].
Table 2 shows some examples of bioactive molecules from natural sources (plants and their by-products and algae), as well as the type of technologies and solvents used in the extraction process.
Sources | Compounds | Technologies (Solvents) | Bioactivities | References |
---|---|---|---|---|
Passion fruit peel | Carotenoids Pectin | MAE,UAE (water, 0live oil sun flower oil) | Antioxidant Antimicrobial Anticancer | [46, 47] |
Vine pruning | Polyphenols | OH, MAE, (water, ethanol) | Antioxidant Anticancer | [48, 49] |
Grape skins | Anthocyanins Polyphenols | OH, MAE, UAE, EAE, PLE (water, eutectic solvents) | Antioxidant | [50, 51, 52, 53, 54, 55] |
Colored potato | Anthocyanins | OH (water) | Antioxidant Antimicrobial Anticancer Neuroprotective | [15] |
Pine bark | Polyphenols | OH, MAE, UAE, SFE (CO2, water, ethanol) | Antioxidant Anticancer Antimicrobial Antihyperglycemic | [13, 56, 57, 58] |
Pine nuts | Polyphenols | PLE, UAE, MAE (water) | Antioxidant | [59] |
Soy beans | Proteins Isoflavones | EAE, UAE, PLE (eutectic solvents, ionic liquid, water, methanol) | Antioxidant Cardioprotective Anticancer | [60, 61, 62, 63] |
Mentha | Polyphenols Essential oil | UAE, SFE, MAE, OH (water, ethanol, methanol) | Antioxidant | [64, 65, 66] |
Tomato by-products | Polyphenols Pectin Fatty acids Carotenoids | MAE, HHP, UAE, PEF, SFE, EAE (hexane, methanol, acetone, ethyl lactate) | Antioxidant Cardioprotective Antihypertensive Antidiabetic Anticancer | [67, 68, 69, 70, 71] |
Apple peels | Pectin Polyphenols | UAE, SFE (water) | Antioxidant | [72, 73] |
Apple seeds | Essential oils polyphenols | PFE, UAE, SFE (CO2, water) | Antioxidant | [74, 75, 76] |
Brewer’s spent grains | Polyphenols, proteins | PEF, UAE, SFE (water, ethanol) | Antioxidant | [77, 78, 79] |
Orange peel | Pectin Polyphenols | PEF, MAE (citric acid) | Antioxidant | [37, 80] |
Moringa leaves | Polyphenols Vitamin C | PLE (water) | Antioxidant | [81] |
Rapeseed oil Guava oil, | Phytosterols, Polyphenols Tocopherols | SFE (CO2, Euctetic solvents) | Anticholesterolemic Antioxidant | [82, 83] |
Roselle seeds Black sesame seeds | Phytosterols | SFE (CO2, ethanol) | Anticholesterolemic Antioxidant | [84, 85] |
Polyphenols Carotenoids Phycobiliproteins | OH; MAE; PEF; UAS; EAE (water, ethanol) | Antioxidant Antimicrobial Anticancer Anti-inflammatory | [86, 87, 88, 89, 90, 91, 92, 93, 94, 95] | |
Carotenoids Lipids | OH; UAE (ethanol) | Antioxidant Anti-inflammatory | [96, 97] | |
Carotenoids Polyphenols | PEF; SFE (CO2, Water, water: ethanol) | Antioxidant Antimicrobial Anticancer Anti-inflammatory | [98, 99, 100, 101] | |
Carotenoids Chlorophylls Polyphenols Proteins Lipids | UAE; PEF; PLE (water, ethanol, dimethyl sulfoxide) | Antioxidant UV-protective Anti-inflammatory Anticancer | [102, 103, 104] | |
Proteins Pigments Lipids Carotenoids Chlorophylls Polyphenols | HVED; HHP; PLE, MAE (water, ethanol, chloroform: methanol) | Antioxidant | [17, 105] | |
Carotenoids | PLE (ethanol) | Antioxidant | [106] | |
Sulfated polysaccharides | Maceration by liquid nitrogen (sodium acetate buffer) | Antioxidant | [42] | |
Fatty acids Polyphenols | PLE (hexane, ethyl acetate, ethanol and ethanol:water) | Antioxidant Anti-atherogenic | [107] | |
Polyphenols | MAE (70% methanol) | Antioxidant Anti-hyperglycemic | [108] | |
Polyphenols | PLE (water, ethanol/water, and methanol/water) | Antioxidant Antiproliferative | [40, 109] | |
Proteins Peptides | EAE (water) | Antioxidant Cardioprotective Anti-inflammatory Anti-diabetic | [110, 111] | |
Phycobiliproteins | UAE (phosphate buffer) | Antioxidant Anticancer Anti-inflammatory | [112, 113] |
Green processes for antioxidants recovery from some plants, algae and by-products.
MAE, Microwave assisted extraction; UAE, Ultrasound assisted extraction; PLE, Pressurized liquid extraction; SFE, Supercritical fluid extraction; HHP, High hydrostatic pressure; EAE, Enzyme assisted extraction; PEF, Pulsed electric field; HVED, High voltage electrical discharges; OH, Ohmic heating.
Currently, phytochemicals are being used in several commercial applications, like nutraceuticals, food supplements, cosmetic products, food coloring agents, among others. As an example
Multiple cosmetics companies use algae extracts and compounds in their formulations, as an active agent, or a moisturizer, excipient, gelling, thickening, dyes, pigments, preservatives, additives, aroma or fragrance agents. For example,
β-Carotene was the first high-value product commercially produced from a microalga
Antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), are considered to be, the first line defense in the cells against reactive species like superoxide radical (·O2). SOD, CAT and GPx are indispensable in the antioxidant defense of the body [118]. SOD is an endogenous enzyme and the most powerful antioxidant in the cell. As a metalloenzyme SOD requires a metal cofactor for its activity (iron,zinc or copper). It catalyzes the conversion of two molecules of ·O2 to hydrogen peroxide (H2O2). The level of superoxide dismutase decrease with the age. Moreover, the SOD deficiency was connected to a number of pathologies in both animals and humans. The daily intake of SOD supplement protect the immune system and slow down aging process. CAT is highly efficient antioxidant enzyme, located primarily in the peroxisomes but absent in mitochondria of mammalian cells. It catalyzes the reduction of H2O2 to water and molecular oxygen, completing the process initiated by SOD. In the mammalian mitochondria cells, where the catalase is absent, the breakdown of the hydrogen peroxide to water and oxygen is carried out by another enzyme the GPx. GPx is an intracellular enzyme, and its activity depends on the micronutrient cofactor selenium [118]. Cabbage, brussels sprouts, and broccoli are natural sources of these enzymes [118].
The protein role in the antioxidant defense system is a result of their direct action as precursors of intracellular formation of glutathione [119]. The antioxidant potential of fruit and vegetable juices and grain products is comparable to the antioxidant potential of milk [119]. Plant proteins are considered the new source of antioxidant peptides [120]. Soy milk is soybean-derived product rich in bioactive peptides and isoflavones. It is one of the most popular milk-substitutes for individuals with lactose-intolerance [121]. Other known plant protein drinks substitutes of caw milk are rice milk and almond milk.
Bioactive peptides are present in many fermented and functional foods. The bioactive peptides usually have between 2 and 20 amino acids residues and exercise their activities only after being released from the main protein. Bioactive peptides can display different activities, e.g. antihypertensive, antioxidant, immunomodulatory, anti-inflammatory or antimicrobial, depending on the sequence and amino acid composition [122]. Agroindustrial by-products and wastes are being used as a source of bioactive peptides. Tomato seeds, containing 28% of protein, were subjected to fermentation to obtain different size of peptides [122]. Many times in fruit processing the main generated waste is the fruit stone. The alternatives for reutilization of these type of waste are few (as fertilizers or fuels). The cherry fruit stone contain high values of protein (up to 39%), and is considered a cheap source for production of bioactive peptides [123]. The obtained peptide fractions had high antioxidant or antihypertensive activities [123]. Phycobiliproteins are water soluble protein found in Rhodophyta (red algae), Cyanobacteria (
Other wastes like, peel, leaves, stem, seeds and roots are generated during harvesting, post-harvesting or processing of plants. These wastes are low-cost source of antioxidant molecules like terpenes, polyphenols, phytosterols and peptides that can exhibit different biological activities including antidiabetic, anti-obesity, antihypertensive, anticancer, antiviral and antibacterial [126].
Terpenes also known as terpenoids or isoprenoids are antioxidant molecules formed by the condensation of two subunits of isoprene (C5H8). Moreover, the terpenes are classified on the basis of the number of isoprene units (Figure 1). Terpenes are the main constituents of essential oils (up to 90%) and are very diverse in structure and compounds. Carotenoids are a class of natural lipid-soluble pigments that are responsible for the red, yellow, and orange colors found in various plants and microorganisms. Carotenoids are tetraterpenes (C-40) classified in two groups xanthophylls (lutein, zeaxanthin, and β-cryptoxanthin) and carotenes (α-carotene, β-carotene, and lycopene). Carotenoids are beneficial for humans and animals demonstrating antioxidant, antidibetic, antihypertensive, anti-inflammatory and anticancer activities [33, 127, 128, 129].
Polyphenol compounds are secondary metabolites produced in plants as a response to different stress conditions. Nowadays more than 8,000 polyphenols are known and more than a half correspond to the group of flavonoids. The main structure of the phenols is the benzene ring with different OH radicals. According to their chemical structure phenolic compounds can be divided in two major groups flavonoid and non-flavonoid. The non-flavonoid group includes the phenolic acids (hydroxybenzoic acids and hydroxycinnamic acids), stilbenes and lignans. The anthocyanins, flavanols, flavonols, flavones, flavanones, isoflavones and tannins are flavonoids [5].
Flavonoid consumption is associated with a reduced risk of coronary heart disease, stroke and cancer. Rich sources of polyphenol compounds in nature are fruits and vegetables, cereals, chocolate, olive oils and beverages such as tea and wine (Table 2). Polyphenols are known for their strong antioxidant properties [5]. The strength of their antioxidant activity depends on their interaction with other molecules. For example the absorption of polyphenols in human body is enchased when there is no sugar molecules attached with them. This means that tea polyphenol have higher absorption than fruit polyphenols because of the high sugar content. Normally from the total consumed amount of polyphenol only 15% -20% are absorbed in the human blood [2]. Moreover, studies demonstrated that the addition of milk to tea, a habit common in the United Kingdom, reduces the absorption of flavonols and diminish their antioxidant effect [130].
Vitamins obtained from fruit and vegetables also act as antioxidants. Examples are vitamin C and vitamin E. Vitamin C, that is ascorbic acid is powerful antioxidant found in citrus fruits and vegetables such as oranges, lemons, as well as tomatoes. Vitamin E is a fat-soluble vitamin found naturally in lipid-rich fruits and vegetables, such as olives, sun flower, and nuts [2].
Phytosterols are natural bioactive compounds belonging to the group of triterpens. Humans must obtain phytosterols from plant-derived foods, such as nuts, seeds, cereals and legumes, vegetable oils, soybean oil, and sunflower oil (examples in Table 2) [126]. The most important and abundant phytosterols are β-sitosterol (carbon structure C-29), campesterol (C-28), and stigmasterol (C-29) [126, 131]. Phytosterols have chemical structures and functions similar to cholesterol, but differ from it by an extra methyl or ethyl group at C-24 or a double bond at the C-22 position [132]. Because of the similarity in the structure, phytosterols can reduce cholesterol absorption in the small intestine and thus decreasing blood cholesterol levels. Additional known bioactivities of the phytosterols are anticholesterolemic, antidiabetic, hepatoprotective, anticancer, antioxidant, antimicrobial and anti-inflammatory [131, 133].
Oxidation is a natural phenomenon of human cells. Several important biological processes need reactive oxygen species (ROS) like superoxide radicals, hydrogen peroxide, hydroxyl radicals and singlet oxygen [134, 135]. Without them, protein phosphorylation, activation of transcriptional factors, apoptosis or cell differentiation would not occur. The problem lays on the formation/degradation imbalance of ROS and/or reactive nitrogen species (RNS) [134, 135]. The cell has intrinsic mechanisms to protect itself from excess of ROS/RNS, but only to an extent. If the threshold levels are overcome, cellular structures can be damaged like protein [134, 135, 136], lipids [134, 135, 137], polysaccharides [134, 135, 138] and nucleic acids [134, 135, 139]. Several cell mechanisms of defense against oxidative stress have been described in the literature [140, 141]. These mechanisms can be divided into enzymatic and non-enzymatic. SOD, CAT, GPx, Thioredoxin (TRX), Peroxiredoxin (PRX), Glutathione transferase (GST) are endogenous enzymatic mechanisms, while All trans retinol 2 (Vitamin A), Ascorbic acid (Vitamin C) and α-Tocopherol (Vitamin E) are non-enzymatic endogenous antioxidant mechanism [141]. SOD catalyzes de dismutation of the superoxide anion free radical into molecular oxygen and hydrogen peroxide [141, 142] (Eqs. (1) and (2)). As described by Younus [142] this reaction is accompanied by an alternate oxidation–reduction of the metal ions present in the active site of SOD.
CAT can use iron or even manganese as a cofactor for its enzymatic reactions that will lead to the degradation or reduction of hydrogen peroxide to water molecules and oxygen. This enzyme competes the detoxification process that SOD initiated (Eqs. (3)-(5))[118, 143, 144].
GTPx encompasses two independent reactions, the first one is the reduction of the enzyme by a hydroperoxide (Eq. (6)) followed by the oxidation to GSH [145].
Trx system is composed by Trx and thioredoxin reductase and NADPH. It is described that Trx uses cysteines at position 32 and 35 for the enzymatic reaction. In the first reaction (Adenosine monophosphate + sulfite + thioredoxin disulphide = 5′-adenylyl+thioredoxin) [141, 146] the N-terminal cysteine of Trx acts on the disulphide bond of the substrate protein, leading to the formation a mixed disulphide bond between Trx and the substrate protein. Following the reaction to the C-terminal cysteine of Trx on the intermediate intermolecular disulphide bond, which will form in a disulphide bond in the oxidized Trx and the breakdown of the disulphide bond in the reduce substrate (Adenosine 3′,5′-bisphosphate + sulfite + thioredoxin disulphide = 3′-phosphoadenylyl sulphate+thioredoxin) [141, 146]. PRX are antioxidant enzyme with the ability to reduce hydroperoxides, organic hydroperoxides and peroxynitrite using Trx as electrons donor (Eq. 8) [141, 147].
The presence of ROS initiates an autocatalytic chain lipid peroxidation of polyunsaturated acids, which leads to the formation of toxic electrophilic species and free radicals. This reaction may lead to the increase of 4-Hydroxynonenal (4HNE). GST catalyze conjugation of lipid aldehydes like 4HNE, with GSH are the major defense against oxidative stress-induced cytotoxicity (Eq. (9)) [141, 148].
It is not clear if oxidative stress is the onset of degenerative diseases [149], but it is well known that it plays a significant role in their progression, like in the case of Alzheimer’s disease or vascular dementia [150]. Oxidative stress is also involved in other diseases like cancer [151, 152], cardiovascular diseases [153], metabolic disorders [154], and even on aging [149, 155]. Therefore, it is necessary to lower the ROS/RNS concentration inside the cell to minimize the effect. Antioxidants can act by different chemical mechanism: hydrogen atom transfer (HAT), single electron transfer (SET) and the ability to chelate transition metals.
Most of the commercially available anti-inflammatory and antioxidant medication present side effects [156], therefore the interest in natural antioxidants has grown considerably for the past years, being the phytochemicals a group of interest.
The characterization of molecules with antioxidant potential is complex, due to the inherent complexity of the oxidative reactions that occurs in cells [156]. There are several methods to determine the antioxidant potential of a particular substrate. Table 3 describes some of the chemical
Method | Description | Determination | References |
---|---|---|---|
2,2-diphenyl-1-picrylhydrazyl (DPPH) | DPPH is a stable free radical that in contact with a substrate that can donate a hydrogen bond forms a non-radical molecule Diphenylpicrylhhydrazine. Scavenging activity mechanism. | Colorimetric | [1] |
2,2`-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) | In the presence of antioxidant ABTS.+ is reduce to ABTS resulting in a decrease in color. Scavenging activity mechanism. | Colorimetric | [157, 158] |
O2−· scavenging activity | This assay is optimized for enzymatic antioxidants and relies on the competition kinetics of O2−· reduction of cytochrome C (probe) and O2−· scavenger (sample). Not suitable for non-enzymatic antioxidants. Scavenging activity mechanism. | Fluorescence | [1] |
H2O2 scavenging activity | A common assay that claims to measure H2O2 scavenging capacity of dietary antioxidants uses horseradish peroxidase to oxidize scopoletin to a nonfluorescent product. In the presence of antioxidants the oxidation is inhibited. Scavenging activity mechanism. | Fluorescence | [1] |
Ferric ion reducing antioxidant power (FRAP) | It is based on the ability of antioxidants to reduce ferric iron. The molecule 2,3,5-triphenyl-1,3,4-triaza-2-azoniacyclopenta-1,4-diene chloride (TPTZ) is reduce to the ferrous form at a low pH. This reduction will result in a color change. Reducing power mechanism. | Colorimetric | [158, 159] |
Cupric ion reducing antioxidant capacity (CUPRAC) | bis(neocuproine)copper(II) chloride (Cu(II)-Nc) chromogenic oxidizing agent can react with a polyphenol. The reactive Ar-OH from the polyphenol are oxidized to quinones and Cu (II)-Nc reduced to a highly colored Cu (I)-Nc chelate. | Colorimetric | [158, 160] |
Oxygen radical absorbance capacity (ORAC) | Assay is based on the oxidation of a fluorescent probe by peroxyl radicals by way of a hydrogen atom transfer (HAT) process. Peroxyl radicals are produced by a free radical initiator, which quenches the fluorescent probe over time. Antioxidants present in the assay work to block the peroxyl radical oxidation of the fluorescent probe until the antioxidant activity in the sample is depleted. The remaining peroxyl radicals destroy the fluorescence of the fluorescent probe. | Fluorescence | [161, 162] |
Total radical-trapping antioxidant potential (TRAP) | It is based on the measurement of the fluorescence decay of R-phytocoerythrin during an oxidation reaction. Antioxidant activity mechanism. | Chemiluminescence quenching | [163, 164] |
Thiobarbituric reactive substances (TBARS) | Lipid peroxidation inhibition. | Colorimetric Fluorescence | [1] |
In vitro assays to evaluate natural substrates antioxidant potential.
The chemical characterization of phytochemicals in terms of their antioxidant capacity is only the first step. It is necessary to perform a second screening using
Several studies have been made regarding the antioxidative properties of phytochemicals, as an example Ferreira-Santos
The third step is to evaluate these molecules
In the literature there are extensive studies regarding phytochemicals impact human health, particularly on the prevention of cardiovascular, metabolic, neurodegenerative and cancer diseases.
Cardiovascular diseases are associated with a multiple risk factors like hypercholesterolemia, hypertension, smoking, diabetes, poor diet, stress and physical inactivity. Usually, vegetables like spinach, citrus fruits, soybean oil, sprouts, peppers, cereals, spices, whole grain, honey, walnuts and black tea can significantly increase the hepatic antioxidant enzymes reduces the risk of cardiovascular diseases. Some specific fruits, vegetables or legumes can prevent cardiovascular disease induced by oxidative stress, due to presence of unique dietary antioxidant components [34].
Already in 1999, a study comprising approximately 100 000 patients in the US evaluated over a period of 7 years the outcome of flavonoid intake. The results demonstrated that flavonoid consumption was associated with lower risk of death with cardiovascular disease [172]. Patel
Hypertension is characterized by high blood pressure leading to cardiac and vascular problems. A study performed in hypertensive rats demonstrated that the intake of
Diabetes mellitus, a chronic metabolic disease, characterized by elevated levels of blood glucose and insufficiency in production and action of insulin is the seventh leading cause of death worldwide. Phytochemicals with antioxidant activity like cinnamic acids, coumarins, diterpenes, flavonoids, lignans, prophenylphenols, monoterpenes, tannins, triterpenes,
Similarly to cardiovascular diseases, the number of reports regarding the benefices of phytochemicals and cancer prevention and treatment are immense. Briefly, it has been reported that curcumin, a polyphenol compound that has anticancer properties, acting on cell cycle regulation, apoptosis, oncogene expression and metastasis [177]. The intake of green tea seem to help in the treatment of patients with low grade B-cell tumors [178, 179]. Another phytochemical that demonstrated positive results is
Neurodegenerative diseases are highly debilitating diseases associated to oxidative stress and inflammatory processes. Several studies have been performed to validate the benefices of phytochemicals on the several neurodegenerative diseases, like Alzheimer’s, Parkinson’s and multiple sclerosis. Flavonoids have a specific role in central nervous system maintaining homeostasis by effecting as antianxiety, anticonvulsant, by modulating neuronal oxidative metabolism, and neurotransmitters [183]. Epigallocatechin-3-galate, a polyphenol present in the tea leaves seems to delay neurons degeneration [184]. A commercial drug which has in its composition Epigallocatechin-3-galate demonstrated to reduce amyloid plaques on an Alzheimer disease model [185, 186]. Another study demonstrated that epigallocatechin-3-galate and tea prevented the loss of cells in substantia nigra in a Parkinson Disease model [187]. In a neuronal cell culture model SH-SY5Y cells, the presence of epigallocatechin-3-galate has a protective effect [187].
In vitro studies for Parkinson’s, quercetin markedly reduced the apoptosis of pheochromocytoma (PC-12) cells and hippocampal neurons. It showed increased cell viability and inhibited ROS and MDA production in H2O2-induced toxicity in PC-12 cells [183].
Once again curcumin demonstrates to have a positive effect in Alzheimer’s disease, as it can bind to amyloid plaques by inhibiting NF-κβ [188]. A different study demonstrated that ethanolic turmeric extract (
Yang
As an example of a carotenoid action, astaxanthin has potent antioxidant, anti-inflammatory and neuroprotective properties. Wu and coworkers [191] suggested that astaxanthin could alleviate brain aging, which may be due to attenuating oxidative stress, ameliorating hippocampus damage and increasing brain derived neurotrophic factor levels, preventing age-related neurodegenerative diseases.
The use of green methodologies and extraction process optimization to obtain highly value molecules with antioxidant properties, like terpenes, polyphenolic, phytosterols, and bioactive peptides, has increased for the past years. The reduction of the environmental footprint and the ability to obtain safe products with high industrial interest is fundamental for the future.
Upon extraction and purification of the added value compounds it is possible to determine their antioxidant potential by several chemical and biological processes.
Plants, algae and by-products or waste products of the food industry are an invaluable source of active molecules with antioxidant properties. It is of upmost interest the discovery/development of new therapeutical molecules for the application in several diseases. Computer-aided drug screening techniques, animal models and clinical trials should be taken into account to further develop this field of research.
There are several natural bioactive compounds already used for the treatment of different diseases (in combination with the conventional drugs), demonstrating good results.
Overall, natural antioxidant obtained from plants and marine resources have high nutritional potential and reveal a fundamental role in promoting human health, as an alternative to synthetic products.
This chapter was funded by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The chapter was also supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (MSCA-RISE; FODIAC; 778388). Pedro Santos is supported by a doctoral advanced training fellowship (call NORTE-69-2015-2015), funded under the scope of Norte2020 (NORTE-08-5369-FSE-000036).
The authors declare no conflict of interest.
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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:42,paginationItems:[{id:"82914",title:"Glance on the Critical Role of IL-23 Receptor Gene Variations in Inflammation-Induced Carcinogenesis",doi:"10.5772/intechopen.105049",signatures:"Mohammed El-Gedamy",slug:"glance-on-the-critical-role-of-il-23-receptor-gene-variations-in-inflammation-induced-carcinogenesis",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"82875",title:"Lipidomics as a Tool in the Diagnosis and Clinical Therapy",doi:"10.5772/intechopen.105857",signatures:"María Elizbeth Alvarez Sánchez, Erick Nolasco Ontiveros, Rodrigo Arreola, Adriana Montserrat Espinosa González, Ana María García Bores, Roberto Eduardo López Urrutia, Ignacio Peñalosa Castro, María del Socorro Sánchez Correa and Edgar Antonio Estrella Parra",slug:"lipidomics-as-a-tool-in-the-diagnosis-and-clinical-therapy",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82440",title:"Lipid Metabolism and Associated Molecular Signaling Events in Autoimmune Disease",doi:"10.5772/intechopen.105746",signatures:"Mohan Vanditha, Sonu Das and Mathew John",slug:"lipid-metabolism-and-associated-molecular-signaling-events-in-autoimmune-disease",totalDownloads:17,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82483",title:"Oxidative Stress in Cardiovascular Diseases",doi:"10.5772/intechopen.105891",signatures:"Laura Mourino-Alvarez, Tamara Sastre-Oliva, Nerea Corbacho-Alonso and Maria G. 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She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:{name:"Kobe College",institutionURL:null,country:{name:"Japan"}}}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. 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He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. 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Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"11",type:"subseries",title:"Cell Physiology",keywords:"Neurodevelopment and Neurodevelopmental Disease, Free Radicals, Tumor Metastasis, Antioxidants, Essential Fatty Acids, Melatonin, Lipid Peroxidation Products and Aging Physiology",scope:"\r\n\tThe integration of tissues and organs throughout the mammalian body, as well as the expression, structure, and function of molecular and cellular components, is essential for modern physiology. The following concerns will be addressed in this Cell Physiology subject, which will consider all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and their interactions: (1) Neurodevelopment and Neurodevelopmental Disease (2) Free Radicals (3) Tumor Metastasis (4) Antioxidants (5) Essential Fatty Acids (6) Melatonin and (7) Lipid Peroxidation Products and Aging Physiology.
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He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. 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